Fake skin patches could deliver helpful genes

Patches of synthetic skin could deliver gene therapies to patients without the need for injections.

Jon Vogel and colleagues at the National Institutes of Health in Bethesda, Maryland, cultured fibroblasts and keratinocytes – the principal cells of the skin – and introduced into their genomes the gene for atrial natriuretic peptide (ANP), which is naturally released by cells in the heart. It reduces blood pressure by dilating blood vessels and lowering blood volume.

They mixed these cells into a jelly-like matrix. The cells in the gel formed layers just like those in human skin. These delicate grafts were then attached to the backs of mice.

Within a few weeks, the grafts were accepted by the mice as normal skin and had started pumping ANP into their bloodstreams. The team used tiny radio transmitters inserted into the animals' arteries to measure blood pressure. These showed the grafts led to a drop in blood pressure, and it stayed low even when the mice were put on a high-salt diet.

Vogel hopes that synthetic skin grafts could be used to deliver genes for proteins that might otherwise be expensive or difficult to administer. "Skin is a good target because it's accessible," he says. "If anything goes wrong you can just remove it."

Human trials are still a few years away, Vogel says. "We hope to test the graft on larger animals, such as pigs, which have skin similar to humans."

The team are working on ways to control or boost the dose that the skin patch delivers. For example, Aa topical cream could be used to promote the gene's activity, increasing protein production. "In the case of diabetes, you could imagine insulin being released at a constant rate," says Vogel. "You could just rub in some cream to control your blood sugar levels."

Jeff Morgan, a cell biologist at Brown University in Providence, Rhode Island, and a member of the first group to look into genetically modified skin grafts, thinks the research is exciting. "This paper is a significant step towards applications in humans," he says.

Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0908882

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